The aim is to obtain detailed understanding of neurotransmitter, hormone and drug actions involving cyclic nucleotides in the nervous system. Growth, differentiation and specialized functions of glial cells as well as neurons will be considered. A specific heat-stabile protein from brain, which is a calcium-dependent regulator of adenylate cyclase and cyclic GMP phosphodiesterase, will be examined for possible involvement in coupling hormone receptors to adenylate cyclase, for alterations in neoplastic transformation of cells, and for participation in the bidirectional control of numerous cell functions by cyclic AMP and cyclic GMP. Results of biochemical studies using primarily glial tumor and neuroblastoma cells in culture will be utilized in studies of the hypothalamus. Mobilization and release of neurotransmitter from axon terminals will be assessed. Quantitative histochemical and immunofluorescence methods are being used in a search for electrophysiological and functional correlates of cyclic nucleotides in the limbic system.